Topical prostaglandin analogues and conjunctival inflammation in uveitic glaucoma.

A pilot study to determine whether topical prostaglandin analogues alter the expression of conjunctival inflammatory markers in patients with uveitic glaucoma.Prospective, single-masked case series of 20 patients with uveitis and secondary raised intraocular pressure. Participants were divided into four groups of five patients dependent on their use of topical medication: (1) prostaglandin analogues only, (2) corticosteroids only, (3) both prostaglandin analogues and corticosteroids, (4) no topical medication. Conjunctival cells were harvested by impression cytology and were examined for inflammatory markers (CD3, CD54, HLA-DR, CCR4, CCR5) by flow cytometry. A tear fluid sample was also examined for inflammatory cytokines (IL-12p70, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IFN-gamma, IL-1beta, IFN-alpha, IFN-beta) by multiplex bead arrays.All groups demonstrated increased markers of conjunctival inflammation. There was no significant difference in levels of any inflammatory markers between the four groups, suggesting that the use of topical prostaglandin analogues does not increase conjunctival levels of inflammation beyond those already seen in uveitis.The use of topical prostaglandins does not appear to induce conjunctival inflammation over that which is already present in patients with uveitic glaucoma. This supports the use of topical prostaglandin analogues in patients with uveitic glaucoma, indicating that their use is unlikely to adversely affect subsequent glaucoma filtration surgery through the induction of chronic conjunctival inflammation

Inferring HIV escape rates from multi-locus genotype data

Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by major histocompatibility complex (MHC) molecules on the surface of virally infected cells and generate an anti-viral response that can kill the infected cells. Virus variants whose protein fragments are not efficiently presented on infected cells or whose fragments are presented but not recognized by CTLs therefore have a competitive advantage and spread rapidly through the population. We present a method that allows a more robust estimation of these escape rates from serially sampled sequence data. The proposed method accounts for competition between multiple escapes by explicitly modeling the accumulation of escape mutations and the stochastic effects of rare multiple mutants. Applying our method to serially sampled HIV sequence data, we estimate rates of HIV escape that are substantially larger than those previously reported. The method can be extended to complex escapes that require compensatory mutations. We expect our method to be applicable in other contexts such as cancer evolution where time series data is also available

Proton beam radiotherapy in the management of uveal melanoma: clinical experience in Scotland

<p>Aim: To evaluate proton-beam radiotherapy (PBRT) in the management of uveal melanoma in Scotland.</p> <p>Methods: A retrospective review was undertaken on all patients receiving PBRT for uveal melanoma (1994–2005). Data obtained included: gender, past ocular/medical history, age, presenting complaint(s), diagnosis, laterality, tumor location/ultrasound characteristics, visual acuity (VA) and intraocular pressure. At post-treatment reviews (3, 6, 12, and 24 months), the following data was obtained: VA, intraocular pressure, tumor appearance and ultrasound characteristics. Mean follow up was 38.8 months.</p> <p>Results: Seventy-six patients were included. Mean age was 64 years; male to female ratio was 1.1:1. Ninety-seven percent demonstrated initial treatment response; 87% had successful control of tumor growth. Mean pre-treatment tumor height was 6.2 mm v.s. 4.8 mm post-irradiation (p < 0.001). Pre-irradiation VA was <3/60 in 18.5% compared with 74% post-irradiation (p < 0.0001). There was a statistically significant association between adverse events (enucleation, metastasis) and greater maximal basal tumor diameter. Eighteen eyes were enucleated. The median survival time was estimated to be 54 months.</p> <p>Conclusion: In our experience, PBRT is a precise, reliable and effective treatment in the management of large, and previously treated uveal melanomas. It prevents enucleation in the majority at short term follow-up.</p&gt

The diffuse neutrino flux from the inner Galaxy: constraints from very high energy gamma-ray observations

Recently, the MILAGRO collaboration reported on the detection of a diffuse multi-TeV emission from a region of the Galactic disk close to the inner Galaxy. The emission is in excess of what is predicted by conventional models for cosmic ray propagation, which are tuned to reproduce the spectrum of cosmic rays observed locally. By assuming that the excess detected by MILAGRO is of hadronic origin and that it is representative for the whole inner Galactic region, we estimate the expected diffuse flux of neutrinos from a region of the Galactic disk with coordinates $-40^{\circ} < l < 40^{\circ}$. Our estimate has to be considered as the maximal expected neutrino flux compatible with all the available gamma ray data, since any leptonic contribution to the observed gamma-ray emission would lower the neutrino flux. The diffuse flux of neutrinos, if close to the maximum allowed level, may be detected by a km$^3$--scale detector located in the northern hemisphere. A detection would unambiguously reveal the hadronic origin of the diffuse gamma-ray emission.Comment: submitted to Astroparticle Physic

Maximum or Minimum Differentiation? An Empirical Investigation into the Location of Firms

We empirically test some implications from location theory using the location of Los Angeles area gasoline stations in physical space and in the space of product attributes. We consider the effect of demand patterns, entry costs, and several proxies for competition -- the total number of stations, the proportion of independent stations, and the proportion of same-brand stations in a market -- on the tendency for a gasoline station to be physically located more or less closely to its competitors. Using an estimation procedure that controls for spatial correlation and controlling for market characteristics as well as non- spatial product attributes, we find that firms locate their stations in an attempt to spatially differentiate their product as general market competition increases. In other words, the incentive to differentiate in order to soften price competition dominates the incentive to cluster locations to attract consumers from rivals. We also find that spatial differentiation increases as stations become more differentiated in other station characteristics.product differentiation, spatial theory, location theory, retail gasoline

Fundamental constraints on particle tracking with optical tweezers

A general quantum limit to the sensitivity of particle position measurements is derived following the simple principle of the Heisenberg microscope. The value of this limit is calculated for particles in the Rayleigh and Mie scattering regimes, and with parameters which are relevant to optical tweezers experiments. The minimum power required to observe the zero-point motion of a levitating bead is also calculated, with the optimal particle diameter always smaller than the wavelength. We show that recent optical tweezers experiments are within two orders of magnitude of quantum limited sensitivity, suggesting that quantum optical resources may soon play an important role in high sensitivity tracking applications